Bacterial vaginosis (BV) is a common condition that is related to alterations in the normal vaginal flora. It is the most common cause of vaginitis in women and has a recurrence rate of approximately 20%-40% at one month after therapy. In addition to the general discomfort associated with the condition, BV has been linked to premature membrane rupture, premature delivery, low birth weight, acquisition of HIV and other STDs, development of pelvic inflammatory disease (PID), and post-operative infections following gynecological procedures.
Although the precise etiology of BV is unknown, the disease itself is associated with the decrease or absence of protective lactobacilli which are normally present in the vagina. Lactobacilli produce lactic acid from glycogen to maintain the vagina's acidic pH. This acidic environment inhibits the growth of other bacterial species typically found in the vagina, albeit at low levels. Vaginal lactobacilli also produce hydrogen peroxide (H2O2), which is toxic to viruses as well as to bacteria in vitro. When lactobacilli are sufficiently absent, bacteria such as Gardnerella vaginalis, Bacteroides spp., Mobiluncus spp., Haemophilus spp., peptostreptococci, Mycoplasma hominis, ureaplasma, and other anaerobes can populate the vaginal tract without difficulty.
Currently approved treatments for BV include administering metronidazole (“MTZ”) 500 mg orally twice a day for 7 days; administering MTZ gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days; administering clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days; administering tinidazole, 2 g orally once daily for 2 days; or administering tinidazole, 1 g orally once daily for 5 days.
Although MTZ remains the primary choice for treating BV in the United States, tinidazole is particularly useful for treating MTZ-resistant G. vaginalis, an organism commonly associated with BV. Despite this utility, tinidazole must be dosed orally, whereas MTZ can be dose intravaginally. Common side effects associated with the oral administration of tinidazole include, but are not limited to, metallic/bitter taste, nausea, anorexia, dyspepsia/cramps/epigastric discomfort, vomiting, constipation, tongue discoloration, stomatitis, diarrhea, decreased appetite, and flatulence.
Thus, there exists a need for novel tinidazole formulations suitable for the treatment of BV and other diseases of the vaginal cavity that respond to or are susceptible to tinidazole (e.g. trichomoniasis) that reduce or alleviate many of the side effects commonly associated with the oral form of the drug. The present disclosure provides such formulations.